CN106474474B - Photo-thermal nano particle based on peptide and photosensitizer, preparation method and application thereof - Google Patents
Photo-thermal nano particle based on peptide and photosensitizer, preparation method and application thereof Download PDFInfo
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- CN106474474B CN106474474B CN201611024269.9A CN201611024269A CN106474474B CN 106474474 B CN106474474 B CN 106474474B CN 201611024269 A CN201611024269 A CN 201611024269A CN 106474474 B CN106474474 B CN 106474474B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0076—PDT with expanded (metallo)porphyrins, i.e. having more than 20 ring atoms, e.g. texaphyrins, sapphyrins, hexaphyrins, pentaphyrins, porphocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/225—Microparticles, microcapsules
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- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Abstract
The invention relates to a photo-thermal nano particle based on peptide and photosensitizer, a preparation method and application thereof. The photo-thermal nano-particles are formed by self-assembling peptide-photosensitizer covalent complexes in a water system; the formed photo-thermal nano particles have the advantages of controllable particle size, stable dispersion in a water system and high photo-thermal conversion efficiency, the photo-thermal conversion efficiency can reach more than 40%, and the photo-thermal nano particles have wide application prospects in the aspects of preparing photo-acoustic imaging reagents, photo-thermal treatment reagents and the like.
Description
Technical Field
The invention belongs to the field of nano biomedicine, and relates to a photo-thermal nano particle based on peptide and a photosensitizer, a preparation method and application thereof.
Background
Photothermal nanoparticles are a new type of nanoparticles that can capture light and convert light energy into heat. The photothermal nanoparticles have wide application prospects, such as the preparation of photoacoustic imaging and photothermal treatment agents. In the photoacoustic imaging technology, the nano particles convert light into heat, and the ultrasonic signals are further generated by expansion caused by the heat, so that the directivity of the light and the high-resolution characteristic of ultrasonic detection are combined, and the advantages of large detection depth, high sensitivity and high safety are shown in the inspection of tumors. Based on the same photothermal conversion process, the photothermal nanoparticles can increase the temperature of cells and tissues around the photothermal nanoparticles, so that the purpose of directionally killing diseased cells is achieved. In contrast to conventional radiation detection and treatment, the visible and near infrared light utilized in photoacoustic imaging and photothermal treatment does not have a direct killing effect on normal cells and tissues. Therefore, the photothermal nanoparticles provide an efficient and safe way for diagnosis and treatment of tumors.
Nanoparticles for photoacoustic imaging and photothermal therapy need to have properties of strong absorption in the near infrared region and high photothermal conversion efficiency. The photo-thermal nanoparticles which are widely researched comprise gold nanoparticles, graphene oxide, carbon nanotubes and the like. These inorganic nanoparticles have greater photothermal conversion efficiency and photostability, but they are not degradable in vivo and long-term safety has not been confirmed. In order to overcome the problem of non-degradability of inorganic nanoparticles, people develop photo-thermal nanoparticles based on high-molecular polymers such as polypyrrole, polyaniline and the like, but the materials also have the problems of difficult surface modification and complex degradation mechanism.
The peptide is an important structural unit naturally existing in organisms, and the amino acid sequence of a peptide molecule determines that the peptide molecule can be self-assembled under certain conditions to form nanoparticles with various morphologies. Not only can peptide molecules self-assemble to form nanoparticles, but also covalent complexes comprising the structure of the peptide molecules can form various ordered structures under the action of the peptide molecules, and the structures have shown some advantages in the delivery of chemotherapeutic drugs and the like. The self-assembled nano particle based on the peptide molecule has the advantages of no immunogenicity, definite chemical structure and small toxic and side effects when being used in the aspect of biological medicine. However, no report has been made on how to design a rational peptide-photosensitizer molecule and prepare photothermal nanoparticles based on the peptide and photosensitizer.
Disclosure of Invention
The invention aims to provide a photo-thermal nano particle based on peptide and photosensitizer, a preparation method and application thereof; the photo-thermal nano particles formed by the invention have the characteristics of stable dispersion in a water system, uniform particle size distribution, controllable size, high photo-thermal conversion efficiency and high biological safety.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides photothermal nanoparticles formed by molecular self-assembly of a peptide-photosensitizer covalent complex.
In the invention, the nano-particles are formed by self-assembling peptide-photosensitizer covalent complexes in an aqueous system, wherein the peptide-photosensitizer covalent complexes are different from the conventional co-assembly form of peptide and photosensitizer molecules by covalent bonding between peptide chains and photosensitizers.
The invention adopts the form of peptide-photosensitizer covalent complex for self-assembly, can form the photo-thermal nano particles with controllable particle size and stable dispersion in a water system, has the outstanding advantage of high photo-thermal conversion efficiency which can reach more than 40 percent, and can be applied to the fields of preparing photo-acoustic imaging reagents, photo-thermal treatment reagents and the like.
According to the invention, the peptide-photosensitizer covalent complex is covalently linked to the peptide chain through an alkyl chain via an amide bond, for example, either to the carbon or to the nitrogen terminus of the peptide chain.
In the present invention, the alkyl chain is mainly used for connecting the photosensitizer molecule and the peptide chain, and may be selected from alkyl chains containing 0 to 10 carbon atoms, such as 0, 1, 2, 3, 4, 5, 7, 9 or 10, and when the number of carbon atoms is 0, there is no alkyl chain between the photosensitizer molecule and the peptide chain.
According to the present invention, in the peptide-photosensitizer covalent complex, the photosensitizer molecules may be hydrophilic and/or hydrophobic photosensitizer molecules, however, photo-thermal nanoparticles formed when hydrophobic photosensitizer molecules are used exhibit greater advantages in photo-thermal conversion efficiency.
In the present invention, the photosensitizer molecule is porphyrin, porphyrin derivative or porphyrin analog, preferably tetraphenylporphyrin, chlorin E6, pyropheophorbide, bacteriochlorophyll, chlorophyll a, tetrahydroxyphenyl chlorin, purpurin, benzo chlorin, naphtho chlorin, keto chlorin, aza chlorin, bacteriochlorin, tolyl porphyrin, benzo bacteriochlorin, phthalocyanine, naphthalocyanine, porphyrene or a mixture of at least two of them, typically but not limited to a mixture of: porphyrins and porphyrin derivatives, bacteriochlorophyll and chlorophyll a, naphthochlorins and ketochlorins.
According to the present invention, the peptide chain in the peptide-photosensitizer covalent complex is an oligopeptide sequence composed of any one, two or three of phenylalanine, tyrosine, tryptophan, glutamine, glutamic acid, aspartic acid, lysine, histidine or arginine.
The peptide chain in the invention selects an oligopeptide sequence with amino acids ranging from 1 to 3, which is beneficial to the formed photothermal nanoparticles to exert greater photothermal conversion efficiency.
In the present invention, the peptide chain may be selected from any one of L-phenylalanine, L-phenylalanine-L-phenylalanine, L-aspartic acid-L-aspartic acid, L-histidine-L-histidine or L-histidine-L-histidine, and is preferably a peptide chain containing L-phenylalanine.
The photo-thermal nano particles are spherical in shape, and the diameters of the photo-thermal nano particles are within the range of 10-200 nm.
Illustratively, the peptide-photosensitizer covalent complexes of the present invention have the structural formula shown below:
in a second aspect, the present invention provides a method for preparing photothermal nanoparticles as described in the first aspect, comprising the steps of:
(1) preparing a solution of the peptide-photosensitizer covalent complex in a good solvent;
(2) and (2) adding the solution obtained in the step (1) into a poor solvent to obtain the photo-thermal nano particles based on the peptide-photosensitizer covalent complex.
In the present invention, the concentration of the peptide-photosensitizer covalent complex in the good solvent in step (1) is 0.1-100mg/mL, for example, 0.1mg/mL, 0.5mg/mL, 1mg/mL, 5mg/mL, 10mg/mL, 20mg/mL, 30mg/mL, 50mg/mL, 60mg/mL, 70mg/mL, 90mg/mL or 100mg/mL, preferably 1-50 mg/mL.
In the present invention, the concentration of the peptide-photosensitizer covalent complex in the poor solvent in step (2) is 0.01 to 20mg/mL, for example, 0.01mg/mL, 0.05mg/mL, 0.1mg/mL, 0.5mg/mL, 1mg/mL, 3mg/mL, 5mg/mL, 8mg/mL, 10mg/mL, 12mg/mL, 15mg/mL, 18mg/mL or 20mg/mL, preferably 0.1 to 15 mg/mL.
In the invention, the good solvent in the step (1) is any one or a mixture of at least two of dimethyl sulfoxide, ethanol, methanol, tetrahydrofuran, dimethylformamide or acetonitrile; the poor solvent in the step (2) is any one or a mixture of at least two of water, phosphate buffer solution, tris-hydrochloric acid buffer solution, acetic acid-ammonium acetate buffer solution, ammonia-ammonium chloride buffer solution or citric acid-disodium hydrogen phosphate buffer solution.
Specifically, the preparation method of the photothermal nanoparticles provided by the invention can comprise the following steps:
(1) preparing a solution of 0.1-100mg/mL of the peptide-photosensitizer covalent complex in a good solvent;
the good solvent is any one or a mixture of at least two of dimethyl sulfoxide, ethanol, methanol, tetrahydrofuran, dimethylformamide or acetonitrile;
(2) adding the solution into a poor solvent, wherein the concentration of the peptide-photosensitizer covalent complex in the poor solvent is 0.01-20mg/mL, so as to obtain the photo-thermal nanoparticles based on the peptide-photosensitizer covalent complex;
the poor solvent is any one or a mixture of at least two of water, phosphate buffer solution, tris-hydrochloric acid buffer solution, acetic acid-ammonium acetate buffer solution, ammonia-ammonium chloride buffer solution or citric acid-disodium hydrogen phosphate buffer solution.
Illustratively, the preparation method of the photo-thermal nano-particles comprises the following steps:
(1) preparing a peptide-photosensitizer covalent complex into a solution of 10mg/mL in dimethyl sulfoxide;
(2) and adding the solution into water, wherein the concentration of the peptide-photosensitizer covalent complex in a poor solvent is 5mg/mL, so as to obtain the photo-thermal nano-particles based on the peptide-photosensitizer covalent complex.
Or, the preparation method of the photo-thermal nano-particles comprises the following steps:
(1) preparing a peptide-photosensitizer covalent complex into a solution of 50mg/mL in ethanol;
(2) and adding the solution into a phosphate buffer solution, wherein the concentration of the peptide-photosensitizer covalent complex in a poor solvent is 10mg/mL, so as to obtain the photo-thermal nano particles based on the peptide-photosensitizer covalent complex.
In a third aspect, the present invention also provides the use of photothermal nanoparticles according to the first aspect of the invention for the preparation of a photothermal therapeutic formulation.
In a fourth aspect, the present invention also provides the use of photothermal nanoparticles according to the first aspect of the present invention for the preparation of a photoacoustic imaging agent.
The photothermal nanoparticles of the present invention are formed by self-assembly of peptide-photosensitizer covalent complexes; wherein the photosensitizer plays a role of absorbing light energy; the peptide molecules are used for regulating and controlling the self-assembly of the photosensitizer, so that the photosensitizer molecules in the formed nanoparticles are in an ordered aggregation state to enhance the conversion of light energy to heat, and the photosensitizer molecules are inhibited from further aggregation to ensure that the obtained nanoparticles are stably dispersed in a water system; compared with the existing photothermal nanoparticles, the photothermal nanoparticles based on the peptide and the photosensitizer have the advantages of definite molecular structure, biodegradability, high biological safety and no immunogenicity, and potential toxic and side effects when the nanoparticles based on the inorganic nanoparticles and the high molecular polymer are applied to a human body are avoided.
Compared with the prior art, the invention has at least the following beneficial effects:
(1) the photo-thermal nano particles provided by the invention have the photo-thermal conversion efficiency of more than 40%;
(2) the photo-thermal nano particles provided by the invention have the advantages of controllable particle size, stable dispersion and biodegradability in a water system, high biological safety and no immunogenicity, and potential toxic and side effects caused by application of inorganic nano particles and high molecular polymers to human bodies are avoided.
Drawings
FIG. 1 is a transmission electron microscope photograph of photothermal nanoparticles of example 1;
FIG. 2 is a graph showing a distribution of particle diameters of photothermal nanoparticles in example 2;
FIG. 3 is a graph of the potential distribution of photothermal nanoparticles of example 3;
FIG. 4 is an atomic force microscope photograph of photothermal nanoparticles of example 4;
FIG. 5 is a graph of the temperature increase of the photothermal nanoparticles of example 5 under illumination;
FIG. 6 is a graph of temperature ramp-up and ramp-down for the photothermal nanoparticles of example 6;
FIG. 7 is a photoacoustic signal of the photothermal nanoparticles of example 7 in solution;
FIG. 8 is a graph of photoacoustic signal intensity for in vivo photoacoustic imaging using photothermal nanoparticles of example 8;
FIG. 9 is a thermal imaging of photothermal nanoparticles of example 9 for photothermal therapy;
FIG. 10 is a graph showing the effect of photothermal nanoparticles of example 10 on cell killing in photothermal therapy;
FIG. 11 is a graph showing the change of tumor volume when the photothermal nanoparticles of example 11 are used for photothermal therapy of a living body.
The present invention is described in further detail below. The following examples are merely illustrative of the present invention and do not represent or limit the scope of the claims, which are defined by the claims.
Detailed Description
The present invention will be described in detail below with reference to examples, but the present invention is not limited to the following examples.
Example 1
Dissolving 2mg of a compound with a structural formula shown in the specification in 1mL of dimethyl sulfoxide to prepare a solution of 5mg/mL, and adding 10mL of water to obtain a dispersion liquid of photo-thermal nanoparticles. A sample is dropped on a copper net, and a transmission electron microscope test is carried out to obtain the structure shown in figure 1, which shows that the photothermal nano particles are spheres with the diameter of about 30 nm.
Example 2
Dissolving 100mg of a compound with a structural formula shown in the specification in 1mL of ethanol to prepare a solution of 100mg/mL, and adding a phosphate buffer solution to enable the concentration of the compound to be 20mg/mL to obtain a photo-thermal nanoparticle dispersion solution. Samples were taken for dynamic light scattering testing and the results are shown in figure 2, which shows that the nanoparticles have a diameter of around 100 nm.
Example 3
Taking 0.1mg of a compound with a structural formula shown in the specification, dissolving the compound in 1mL of methanol to prepare a solution of 0.1mg/mL, adding a trihydroxymethylaminomethane-hydrochloric acid buffer solution to enable the concentration of the compound to be 0.01mg/mL, obtaining a dispersion liquid of photo-thermal nanoparticles, and testing the particle size of the dispersion liquid to be about 10 nanometers. The sample was subjected to a potential test, and the results are shown in FIG. 3, which indicates that the potential of the nanoparticles was around-20 mV.
Example 4
Dissolving 10mg of a compound with a structural formula shown in the specification in 1mL of tetrahydrofuran to prepare a solution of 10mg/mL, and adding an acetic acid-ammonium acetate buffer solution to enable the concentration of the compound to be 1mg/mL to obtain a photo-thermal nanoparticle dispersion solution. A sample is loaded on the surface of the mica sheet for atomic microscope test, and the result is shown in figure 4, which shows that the nano particles are spheres with the diameter of about 200 nanometers.
Example 5
Dissolving 2mg of a compound with a structural formula shown in the specification in 1mL of acetonitrile to prepare a solution of 2mg/mL, and adding an ammonia-ammonium chloride buffer solution to enable the concentration of the compound to be 0.2mg/mL to obtain a dispersion liquid of photo-thermal nanoparticles. 1mL of a sample of 0.2mg/mL is placed in a square cuvette of 1 cm, irradiation is carried out by using a laser with a wavelength of 700 nm, the laser power is 0.2W/cm, pure water is used as a control group, and a temperature detector is used for testing the change of the solution temperature, and the result is shown in FIG. 5, which shows that the nano particles can rapidly convert light energy into heat under the irradiation of the laser, and the photothermal conversion efficiency is 80%.
Example 6
Dissolving 5mg of a compound with a structural formula shown in the specification in 1mL of dimethylformamide to prepare a solution of 5mg/mL, and adding a citric acid-disodium hydrogen phosphate buffer solution to enable the concentration of the compound to be 1mg/mL, thereby obtaining a dispersion solution of photo-thermal nanoparticles. 1mL of a sample with the concentration of 1mg/mL is placed in a square cuvette with the concentration of 1 cm, laser with the wavelength of 650 nm is used for irradiation, the laser power is 0.2W/square cm, the laser is turned off after 10 minutes of irradiation, and the temperature detector is used for testing the change of the solution temperature in the whole process, so that the result is shown in figure 6, which shows that the nano particles can rapidly convert light energy into heat under the laser irradiation, and the photothermal conversion efficiency is calculated to be 46%.
Example 7
Dissolving 5mg of a compound with a structural formula shown in the specification in 1mL of dimethyl sulfoxide to prepare a solution of 5mg/mL, and adding water to enable the concentration of the compound to be 0.5mg/mL, thereby obtaining a photo-thermal nanoparticle dispersion liquid. The photothermal conversion efficiency was tested to be 40%. A sample of 0.5mg/mL was subjected to photoacoustic imaging testing, and the results are shown in FIG. 7, which shows that the nanoparticles can generate photoacoustic signals under laser irradiation.
Example 8
Dissolving 5mg of a compound with a structural formula shown in the specification in 1mL of ethanol to prepare a solution of 5mg/mL, and adding water to enable the concentration of the compound to be 0.5mg/mL, thereby obtaining a photo-thermal nanoparticle dispersion liquid. 200 microliter of a sample of 0.5mg/mL is injected into a tumor-bearing mouse through tail vein, the mouse is placed in a photoacoustic imager for testing after 24 hours, and the result is shown in figure 8, wherein the photoacoustic signal at the tumor part is strong, and the photoacoustic signal in normal tissues is weak, which indicates that the nanoparticles are enriched at the tumor part in the living body and can display the position of the tumor.
Example 9
The photothermal nanoparticles prepared as in example 2 were prepared as a 1mg/mL sample, 200 μ l of the sample was injected into a tumor-bearing mouse through the tail vein, the tumor site was irradiated with laser light having a wavelength of 700 nm after 24 hours, the laser power was 0.2 w/cm, and the temperature change of the mouse was detected by a thermal imager during the irradiation, and the result is shown in fig. 9, which indicates that the temperature of the tumor portion was increased, but the other portions were not significantly changed.
Example 10
The photothermal nanoparticles prepared in example 8 were incubated with breast cancer cell MFC-7, the concentration of the photothermal nanoparticles in the culture solution was 0.05mg/mL, the cells were irradiated with laser light having a wavelength of 700 nm for 2 minutes after 24 hours, the laser power was 0.5 w/cm, and after the irradiation, incubation was continued for 24 hours and cell activity test was performed, and as a result, as shown in fig. 10, the cell activity by photothermal treatment was significantly decreased, while the cell activity without nanoparticle treatment was not significantly changed.
Example 11
The nanoparticles prepared in example 1 were taken and prepared into a 0.8mg/mL solution in 5% aqueous glucose. 20 mice were taken and divided into 4 groups: control group, laser only group, nanoparticle + laser group (photothermal treatment group). Only mice of the nanoparticle group and the nanoparticle + laser group were injected with 200 μ l of nanoparticles through the tail vein, tumors were irradiated with laser light of 635 nm wavelength for 10 minutes after 24 hours, and changes in tumor volume of the mice were tested every other day after irradiation, with the results shown in fig. 11. The results show that the tumor of the photothermal treatment group is well inhibited, while the tumors of other groups have no obvious change, which shows that the nanoparticles can well inhibit the tumor when used for photothermal treatment.
The applicant states that the product and the detailed preparation method of the present invention are illustrated by the above examples, but the present invention is not limited to the above product and the detailed preparation method, i.e. the present invention is not meant to be implemented by relying on the above product and the detailed preparation method. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
In addition, any combination of the various embodiments of the present invention is also possible, and the same should be considered as the disclosure of the present invention as long as it does not depart from the spirit of the present invention.
Claims (9)
1. Photothermal nanoparticles having a photothermal conversion efficiency of 40% or more, wherein the photothermal nanoparticles are formed by molecular self-assembly of a peptide-photosensitizer covalent complex;
the photosensitizer molecule is any one or a mixture of at least two of pyropheophorbide, bacteriochlorophyll, chlorophyll a, tetrahydroxyphenyl chlorin, purpurin, benzo chlorin, naphtho chlorin, keto chlorin, aza chlorin, bacteriochlorin, tolyl porphyrin, benzo bacteriochlorin, phthalocyanine, naphthalocyanine, porphyrene or reversed porphyrin;
the peptide chain is any one of L-phenylalanine, L-phenylalanine-L-phenylalanine, L-aspartic acid-L-aspartic acid, L-histidine-L-histidine or L-histidine-L-histidine;
the peptide-photosensitizer covalent complex is covalently linked to the carbon end or the nitrogen end of a peptide chain through an alkyl chain and an amido bond by photosensitizer molecules;
the alkyl chain contains 0 to 10 carbon atoms;
the preparation method of the photo-thermal nano-particles comprises the following steps:
(1) preparing a solution of the peptide-photosensitizer covalent complex in a good solvent;
(2) adding the solution obtained in the step (1) into a poor solvent to obtain photo-thermal nano particles based on the peptide-photosensitizer covalent compound;
the good solvent in the step (1) is any one or a mixture of at least two of dimethyl sulfoxide, ethanol, methanol, tetrahydrofuran, dimethylformamide and acetonitrile;
the poor solvent in the step (2) is any one or a mixture of at least two of water, phosphate buffer solution, tris-hydrochloric acid buffer solution, acetic acid-ammonium acetate buffer solution, ammonia-ammonium chloride buffer solution or citric acid-disodium hydrogen phosphate buffer solution.
2. The method of preparing photothermal nanoparticles of claim 1 comprising the steps of:
(1) preparing a solution of the peptide-photosensitizer covalent complex in a good solvent;
(2) adding the solution obtained in the step (1) into a poor solvent to obtain photo-thermal nano particles based on the peptide-photosensitizer covalent compound;
the good solvent in the step (1) is any one or a mixture of at least two of dimethyl sulfoxide, ethanol, methanol, tetrahydrofuran, dimethylformamide and acetonitrile;
the poor solvent in the step (2) is any one or a mixture of at least two of water, phosphate buffer solution, tris-hydrochloric acid buffer solution, acetic acid-ammonium acetate buffer solution, ammonia-ammonium chloride buffer solution or citric acid-disodium hydrogen phosphate buffer solution.
3. The method of claim 2, wherein the concentration of the peptide-photosensitizer covalent complex of step (1) in the good solvent is 0.1-100 mg/mL.
4. The method of claim 3, wherein the concentration of the peptide-photosensitizer covalent complex of step (1) in the good solvent is 1-50 mg/mL.
5. The method of claim 2, wherein the concentration of the peptide-photosensitizer covalent complex in the poor solvent of step (2) is 0.01-20 mg/mL.
6. The method of claim 5, wherein the concentration of the peptide-photosensitizer covalent complex in the poor solvent of step (2) is 0.1-15 mg/mL.
7. Method according to one of claims 2 to 6, characterized in that the method comprises the following steps:
(1) preparing a solution of 0.1-100mg/mL of the peptide-photosensitizer covalent complex in a good solvent;
the good solvent is any one or a mixture of at least two of dimethyl sulfoxide, ethanol, methanol, tetrahydrofuran, dimethylformamide or acetonitrile;
(2) adding the solution into a poor solvent, wherein the concentration of the peptide-photosensitizer covalent complex in the poor solvent is 0.01-20mg/mL, so as to obtain the photo-thermal nanoparticles based on the peptide-photosensitizer covalent complex;
the poor solvent is any one or a mixture of at least two of water, phosphate buffer solution, tris-hydrochloric acid buffer solution, acetic acid-ammonium acetate buffer solution, ammonia-ammonium chloride buffer solution or citric acid-disodium hydrogen phosphate buffer solution.
8. Use of the photothermal nanoparticles of claim 1 for the preparation of a photothermal therapeutic formulation.
9. Use of photothermal nanoparticles according to claim 1 for the preparation of a photoacoustic imaging formulation.
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